A number of lines of evidence strongly suggest that the disposition kinetics of digoxin are determined largely by the activity of the MDR1 gene product, the P-glycoprotein efflux pump. Recent studies in human subjects indicate that expression of MDR1 can vary 50-fold among individuals and in animal models is induced to a variable extent by exposure to environmental carcinoogens such as those contained in tobacco smoke. The overall objective of this study, therefore, is to determine the distrubition of P-glycoprotein-dependent efflux mechanisms in the disposition of digoxin in a population of human subjects (smokers and nonsmokers).